Re: Intravesical rAd-IFNα/Syn3 for Patients with High-Grade, bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study

Autor: Brant A. Inman, Michael Woods, Kenneth Ogan, Robert L. Grubb, Robert S. Svatek, David Sawutz, Leonard G. Gomella, F. Peter Treasure, Yair Lotan, Lawrence Karsh, Trinity J. Bivalacqua, Seth P. Lerner, Neal D. Shore, Stephen A. Boorjian, Nigel Parker, Alan Boyd, Matthew I. Milowsky, Daniel J. Canter, Tracy M. Downs, Tracey L. Krupski, Gillian Gregory, Seppo Ylä-Herttuala, Colin P.N. Dinney, Ashish M. Kamat
Rok vydání: 2018
Předmět:
Male
Cancer Research
medicine.medical_treatment
030232 urology & nephrology
Phases of clinical research
Disaccharides
law.invention
Neoplasm Recurrence
0302 clinical medicine
Randomized controlled trial
law
Fatigue
Aged
80 and over
ORIGINAL REPORTS
Middle Aged
Recombinant Proteins
Administration
Intravesical
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
BCG Vaccine
Female
medicine.symptom
Erratum
Non muscle invasive
medicine.drug
medicine.medical_specialty
Recombinant Fusion Proteins
Urology
Genetic Vectors
Alpha interferon
Interferon alpha-2
Adenoviridae
Cystectomy
03 medical and health sciences
Refractory
medicine
Nocturia
Dysuria
Humans
Neoplasm Invasiveness
Adverse effect
Interferon alfa
Aged
Bladder cancer
business.industry
Interferon-alpha
Cholic Acids
Genetic Therapy
medicine.disease
Urination Disorders
Surgery
Urinary Bladder Neoplasms
Drug Resistance
Neoplasm
Neoplasm Grading
Neoplasm Recurrence
Local
business
BCG vaccine
Zdroj: Journal of Urology. 200:1164-1164
ISSN: 1527-3792
0022-5347
Popis: Purpose Many patients with high-risk non–muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd–IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd–IFNα/Syn3 (randomly assigned 1:1 to 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd–IFNα/Syn3 (1 × 1011 vp/mL, n = 21; 3 × 1011 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd–IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd—IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.
Databáze: OpenAIRE
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